Preparation and anticoagulant activity of phosphosulfomannan PI-88

Yu, Guangli
Gunay, Nur Sibel
Linhardt, Robert J.
Toida, Toshihiko
Fareed, Jawed
Hoppensteadt, Debra A.
Shadid, Hazar
Ferro, Vito
Li, Caiping
Fewings, Kym
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Preparation and anticoagulant activity of phosphosulfomannan PI-88, G. Yu, N.S Gunay, R.J Linhardt, T. Toida, J. Fareed, D.A. Hoppensteadt, H. Shadid, V. Ferro, C. Li, K. Fewings, M.C. Palermo, D. Podger, European Journal of Medicinal Chemistry, 37, 783-791, 2002.
A yeast-derived phosphomannan mixture was chemically sulfonated and the composition and structure of the product mixture was studied. This phosphosulfomannan mixture, PI-88, is currently under clinical evaluation as an anti-cancer agent. Analysis using capillary electrophoresis demonstrated that PI-88 was a multi-component mixture. Gel permeation chromatography provided four fractions of PI-88 that contained components which differed in size from disaccharide to hexasaccharide, and by degree of sulfation. These fractions were characterised by spectroscopic and chromatographic methods and the structure of PI-88 is that expected based on the structure of the phosphomannan starting material. The anticoagulant activity of these fractions was evaluated and the structural requirements for activity are described.
European Journal of Medicinal Chemistry, 37, 783-791
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The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Rensselaer Polytechnic Institute, Troy, NY
European Journal of Medicinal Chemistry